Water → HCID 58298436, compound

HRID 604978Notes

Reaction equation

HRID 604978 reaction equation
[BH4-].[Li+].[C:3]([O:7][C:8]([N:10]1[C:14](=[O:15])[C@H:13]([CH:16]([CH3:18])[CH3:17])[CH2:12][C@H:11]1[C:19](OCC1C=CC=CC=1)=[O:20])=[O:9])([CH3:6])([CH3:5])[CH3:4].O>O1CCCC1.C(OCC)(=O)C.C(O)C>[C:3]([O:7][C:8]([N:10]1[C@H:11]([CH2:19][OH:20])[CH2:12][C@@H:13]([CH:16]([CH3:17])[CH3:18])[C:14]1=[O:15])=[O:9])([CH3:6])([CH3:5])[CH3:4]

Participants

7

Reactant 3

HCID 962WaterHCID 4148881Lithium borohydrideHCID 58298427HCID 58298427, compound

Product 1

HCID 58298436HCID 58298436, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
10 °C

Procedure

A suspension of 27 g of lithium borohydride in 15 mL of anhydrous tetrahydrofuran is cooled to 10° C. and a solution of 15.4 g of (2S,4S)-4-isopropyl-5-oxo-pyrrolidine-1,2-dicarboxylic acid-2-benzyl ester-1-tert-butyl ester in 80 mL of tetrahydrofuran is added within 2 hours. The resulting suspension is warmed to 40° C. and stirred for a further 3 hours. Water (800 mL) is then added and the mixture filtered. The solid is then suspended in 700 mL of tetrahydrofuran and heated to reflux for 75 minutes. After this time the mixture is cooled to 25° C. and filtered. The filtrate is treated slowly with 500 mL of a 1.0 M solution of oxalic acid in water at room temperature. The resulting suspension is filtered and the solid washed with 500 mL of tetrahydrofuran. The solvent is then removed from the filtrate to provide an oil. The oil is re-dissolved in a mixture of 630 mL of ethyl acetate and 0.07 L of ethanol at elevated temperature and the slightly cloudy solution filtered. The clear solution is cooled to −25° C. and the resulting suspension stirred for 2 hours. The solid is collected by filtration, washed with ethyl acetate and dried to give (3S,5S)-5-hydroxymethyl-3-isopropyl-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester.

Workup

  1. temperatureThe resulting suspension is warmed to 40° C.
  2. filtrationthe mixture filtered
  3. temperatureheated
  4. temperatureto reflux for 75 minutes
  5. temperatureAfter this time the mixture is cooled to 25° C.
  6. filtrationfiltered
  7. additionThe filtrate is treated slowly with 500 mL of a 1.0 M solution of oxalic acid in water at room temperature
  8. filtrationThe resulting suspension is filtered
  9. washthe solid washed with 500 mL of tetrahydrofuran
  10. customThe solvent is then removed from the filtrate
  11. customto provide an oil
  12. filtrationthe slightly cloudy solution filtered
  13. temperatureThe clear solution is cooled to −25° C.
  14. stirringthe resulting suspension stirred for 2 hours
  15. filtrationThe solid is collected by filtration
  16. washwashed with ethyl acetate
  17. customdried

Sources & evidence

ORD record
ord-c937cb871654468591a28aa4a5007d7b
Source dataset
uspto-grants-2011_03
Patent number
US07910774B2

Reaction notes

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